Fatty acid uptake activates an AXL-CAV1-β-catenin axis to drive melanoma progression.

ABSTRACT: Interaction between the tumor microenvironment and cancer cell plasticity drives intratumor phenotypic heterogeneity and underpins disease progression and nongenetic therapy resistance. Phenotype-specific expression of the AXL receptor tyrosine kinase is a pivotal player in dormancy, invasion, and resistance to treatment. However, although the AXL ligand GAS6 is present within tumors, how AXL is activated in metastasizing cells remains unclear. Here, using melanoma as a model, we reveal that AXL is activated by exposure to human adipocytes and to oleic acid, a monounsaturated fatty acid abundant in lymph and in adipocytes. AXL activation triggers SRC-dependent formation and nuclear translocation of a β-catenin-CAV1 complex required for melanoma invasiveness. Remarkably, only undifferentiat

SUBMITTER: Chocarro-Calvo A 

PROVIDER: S-EPMC11960706 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature